The overall aim of the proposed research program is to study various metabolic activation and inactivation processes involved in carcinogenesis by various chemicals. Metabolic N-hydroxylation of aromatic amines and amides, dealkylation of dialkylnitrosamines, epoxidation of polycyclic aromatic hydrocarbons and aflatoxin B1 are oxidative activation steps mediated via cytochrome P-450 dependent mixed function oxidase systems present in the endoplasmic reticulum of liver and several other tissues of many animals. It is proposed to solubilize, purify and characterize these microsomal P-450 cytochromes. Reconstitution studies with these puified P-450 cytochromes and NADPH-cytochrome P-450 reductase for various carcinogen oxidations would enable us to know whether activation and inactivation processes are mediated via the same cytochrome P-450. Role of cytochrome b5, other flavoproteins and phospholipids present in the endoplasmic reticulum will also be investigated in the metabolism of various carcinogens. Presence of modified P-450 cytochromes (acetylated, methylated or phosphorylated) and its effect on carcinogen oxidation will also be investigated.